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Safety and Efficacy Study of rhPTH(1-84) in Subjects With Hypoparathyroidism

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ClinicalTrials.gov Identifier: NCT03364738
Recruitment Status : Not yet recruiting
First Posted : December 7, 2017
Last Update Posted : December 7, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

This study is open to adults with hypoparathyroidism who complete the SHP634-101 study (PARALLAX Study). The purpose of this study is to see if rhPTH(1-84) is safe and effective in adults with hypoparathyroidism who previously participated in the SHP634-101 study. All participants enrolled in this study will receive rhPTH(1-84) once-daily for 52 weeks via an injection.

Patients who complete the SHP634-101 study will have the option to screen for this extension study.


Condition or disease Intervention/treatment Phase
Hypoparathyroidism Biological: rhPTH(1-84) Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Study Investigating the Safety and Efficacy of rhPTH(1-84) in Subjects With Hypoparathyroidism
Anticipated Study Start Date : December 30, 2017
Estimated Primary Completion Date : April 27, 2020
Estimated Study Completion Date : April 27, 2020

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: rhPTH(1-84)
Participants will receive rhPTH(1-84) subcutaneous (SC) injection in the thigh (alternate thigh every day) once daily (QD) of an escalating dose from 50 microgram (mcg) to a maximum of 100 mcg increased in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining albumin-corrected serum calcium (ACSC) levels in the range of 2-2.25 millimoles per liter (mmol/L) (8.0-9.0 milligrams per deciliter [mg/dL]). Once a participant achieves a stable ACSC (2-2.25 mmol/L [8.0-9.0mg/dL]) and has minimized supplement doses, they will be maintained at that dose of rhPTH(1-84). If ACSC is greater than (>) 2.25 mmol/L (>9.0 mg/dL), a starting dose of 25 mcg will be administered.
Biological: rhPTH(1-84)
Participants will receive rhPTH(1-84) SC injection in the thigh (alternate thigh every day) QD.


Outcome Measures

Primary Outcome Measures :
  1. Proportion of Participants With Total Serum Calcium (Albumin-corrected) Values in the Range of 7.5 mg/dL (1.875 mmol/L)- Upper Limit of Normal (ULN) at Visit 6 (Week 24) [ Time Frame: Week 24 ]
    Total serum calcium (albumin-corrected) levels will be assessed.

  2. Proportion of Participants With Total Serum Calcium (Albumin-corrected) Values in the Range of 7.5 mg/dL (1.875 mmol/L)- Upper Limit of Normal (ULN) at Visit 9 (Week 52) [ Time Frame: Week 52 ]
    Total serum calcium (albumin-corrected) levels will be assessed.

  3. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From start of treatment up to Week 56 ]
    An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) is any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital abnormality/birth defect; is an important medical event.

  4. Number of Participants With Clinically Significant Change in Laboratory Safety Data Reported as an Adverse Event [ Time Frame: From start of treatment up to Week 52 ]
    Laboratory safety data includes clinical chemistry, hematology, and urinalysis.

  5. Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as an Adverse Event [ Time Frame: Week 52 ]
    Vital signs include body temperature, heart rate and systolic and diastolic blood pressure.

  6. Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters [ Time Frame: From start of treatment up to Week 52 ]
    Twelve-lead ECGs will be performed in triplicate with a minimum 2-minute gap between traces. The participant must be resting in the supine position for at least 5 minutes before collecting the ECG

  7. Measurements of Estimated Glomerular Filtration Rate (eGFR) (Calculated From Serum Creatinine) [ Time Frame: Week 52 ]
    Estimated glomerular filtration rate (eGFR) will be calculated using the chronic kidney disease epidemiology (CDK-epi) formula.

  8. Change From Baseline in Anti-parathyroid Hormone (Anti-PTH) antibodies at Week 24 [ Time Frame: Baseline, Week 24 ]
    Blood samples for antibody testing will be collected at least 14 hours after dosing.

  9. Change From Baseline in Anti-parathyroid Hormone (Anti-PTH) antibodies at Week 52 [ Time Frame: Baseline, Week 52 ]
    Blood samples for antibody testing will be collected at least 14 hours after dosing.


Secondary Outcome Measures :
  1. Change From Baseline in Albumin Corrected Serum Calcium (ACSC) Concentration [ Time Frame: Baseline, Week 4, 8, 16, 24, 32, 40 and 52 ]
    Total serum calcium (albumin-corrected) levels will be assessed.

  2. Change From Baseline in Serum Phosphate Concentration [ Time Frame: Baseline, Week 4, 8, 16, 24, 32, 40 and 52 ]
    Serum phosphate concentration will be assessed.

  3. Change From Baseline in Albumin Corrected Serum Calcium (ACSC)-Phosphate Product [ Time Frame: Baseline, Week 4, 8, 16, 24, 32, 40 and 52 ]
    ACSC-phosphate product will be assessed.

  4. Change From Baseline in 24-hour Urine Calcium Excretion [ Time Frame: Baseline, Week 16, 32 and 52 ]
    24-hour urine calcium excretion will be assessed.

  5. Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose [ Time Frame: Baseline, Week 4, 8, 16, 24, 32, 40 and 52 ]
    Prescribed supplemental oral calcium dose will be assessed.

  6. Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose [ Time Frame: Baseline, Week 4, 8, 16, 24, 32, 40 and 52 ]
    Prescribed supplemental active vitamin D dose will be assessed.

  7. Percentage Change From Baseline in Measurements of Serum Bone-specific Alkaline Phosphatase [ Time Frame: Baseline, Week 16, 32 and 52 ]
    Serum bone-specific alkaline phosphatase will be assessed.

  8. Percentage Change From Baseline in Measurements of Procollagen Type I N-terminal Propeptide [ Time Frame: Baseline, Week 16, 32 and 52 ]
    Procollagen type I N-terminal propeptide will be assessed.

  9. Percentage Change From Baseline in Measurements of C-terminal Telopeptide of Type 1 Collagen [ Time Frame: Baseline, Week 16, 32 and 52 ]
    C-terminal telopeptide of type 1 collagen will be assessed.

  10. Percentage Change From Baseline in Measurements of N-terminal Telopeptide of Type 1 Collagen [ Time Frame: Baseline, Week 16, 32 and 52 ]
    N-terminal telopeptide of type 1 collagen will be assessed.

  11. Percentage Change From Baseline in Measurements of Total Osteocalcin [ Time Frame: Baseline, Week 16, 32 and 52 ]
    Total osteocalcin will be assessed.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • An understanding, ability, and willingness to fully comply with study procedures and restrictions
  • Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
  • Previously completed the SHP634-101 (NCT02781844) study, including the 30-day follow-up.
  • Male or non-pregnant, non-lactating female subjects who agree to comply with applicable contraceptive requirements of the protocol or females of non-childbearing potential.

Exclusion Criteria:

  • Received investigational study drug, aside from that received in study SHP634-101 (NCT02781844), within 3 months prior to the screening visit.
  • Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine (with exception of the condition under study), or neurologic system(s) or psychiatric disease, that in the opinion of the investigator, would make the subject unsuitable for this study.
  • Received parathyroid hormone (PTH), PTH analog, or parathyroid hormone fragment 1-34 [PTH(1-34)] treatment within the last 30 days from the screening visit.
  • Subjects with a history of parathyroid hormone intolerance, based on investigator determination.
  • Any disease that might affect calcium metabolism or calcium-phosphate homeostasis as determined by the investigator other than hypoparathyroidism, including but not limited to, active hyperthyroidism; poorly controlled insulin-dependent diabetes mellitus or type 2 diabetes mellitus; severe and chronic cardiac, liver or renal disease; Cushing's syndrome; neuromuscular disease such as rheumatoid arthritis; myeloma; pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy, bone metastases or a history of skeletal malignancies; primary or secondary hyperparathyroidism; a history of parathyroid carcinoma; hypopituitarism, acromegaly; or multiple endocrine neoplasia types 1 and 2 .
  • Subjects who are at increased baseline risk for osteosarcoma such as subjects with Paget's disease of bone or unexplained elevations of alkaline phosphatase, young adult subjects with open epiphyses, subjects with hereditary disorders predisposing to osteosarcoma or subjects with a prior history of external beam or implant radiation therapy involving the skeleton.
  • Use of the following medications prior to administration of investigational product within:

    1. 30 days-loop diuretics, lithium, systemic corticosteroids (medical judgment is required by the investigator. Primarily high doses of systemic corticosteroids [example (eg), prednisone] should be excluded. Stable doses of hydrocortisone [eg, as treatment for Addison's disease] may be acceptable).
    2. 3 months-cinacalcet hydrochloride
    3. 6 months-fluoride tablets, oral bisphosphonates, methotrexate, growth hormone, digoxin
    4. 12 months-intravenous bisphosphonates, drug or alcohol abuse, as determined by the investigator
  • Presence of any clinically significant results from laboratory tests, vital signs assessments, or electrocardiograms (ECG), that in the opinion of the investigator, would make the subject unsuitable for this study.
  • Any medical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for this study.
  • History of a clinically significant illness during the 4 weeks prior to dosing, that in the opinion of the investigator, would make the subject unsuitable for this study.
  • History of any clinically significant surgery or procedure within 8 weeks of first dose, as determined by the investigator or expected to undergo a major surgical procedure during the trial.
  • History of an allergic response(s) to PTH, PTH analogs, or PTH(1-34), or other clinically significant allergies, that in the opinion of the investigator, would make the subject unsuitable for this study.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03364738


Contacts
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com

Sponsors and Collaborators
Shire
Investigators
Study Director: Shire Physician Shire
More Information

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT03364738     History of Changes
Other Study ID Numbers: SHP634-404
2017-003067-36 ( EudraCT Number )
First Posted: December 7, 2017    Key Record Dates
Last Update Posted: December 7, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hypoparathyroidism
Parathyroid Diseases
Endocrine System Diseases